Electrochemical detection is attractive because it provides high sensitivity, small dimensions, low cost, fast response, and compatibility with microfabrication technologies. (See, e.g., Hughes et al., Science, 254: 74-80 (1991); Mir et al., Electrophoresis, 30: 3386-3397 (2009); Trojanowicz, Anal. Chim. Acta, 653: 36-58 (2009); and, Xu et al., Talanta, 80:8-18 (2009).) These characteristics have led to the development of a variety of sensors based on amperometric, potentiometric or impedimetric signals and their assembly into arrays for chemical, biochemical and cellular applications. (See, e.g., Yeow et al., Sensors and Actuators B 44: 434-440 (1997); Martinoia et al., Biosensors & Bioelectronics, 16: 1043-1050 (2001); Hammond et al., IEEE Sensors J., 4: 706-712 (2004); Milgrew et al., Sensors and Actuators B 103: 37-42 (2004); Milgrew et al., Sensors and Actuators B, 111-112: 347-353 (2005); Hizawa et al., Sensors and Actuators B, 117: 509-515 (2006); Heer et al., Biosensors and Bioelectronics, 22: 2546-2553 (2007); Barbaro et al., Sensors and Actuators B, 118: 41-46 (2006); Anderson et al., Sensors and Actuators B, 129: 79-86 (2008); Rothberg et al., U.S. patent publication 2009/0127589; and, Rothberg et al., U.K. patent application GB24611127.) Typically in such systems, analytes are randomly distributed among an array of confinement regions, such as microwells (also referred to herein as “wells”) or reaction chambers, and reagents are delivered to such regions by a fluidics system that directs flows of reagents through a flow cell containing the sensor array. Microwells in which reactions take place, as well as empty wells where no reactions take place, may be monitored by one or more electronic sensors associated with each of the microwells.
Such systems are subject to a host of interrelated phenomena that make highly sensitive measurements challenging. Such phenomena include non-optimal temperature for biology reaction efficiency, thermal gradients across the sensor arrays and flow cells, and components of the system which are not in thermal equilibrium. These phenomena affect the quality of signals collected.
Currently, the common practice to control these phenomena includes relying on the fluid from the fluidics system to reduce the overall surface chip temperature, using smaller semiconductor sensors that run at a lower temperature, incorporating a passive machine heat sink (e.g., metal conductor), and adding an active heat sink (e.g., cooling fan). Other common techniques include using conventional temperature control devices, such as a Peltier device or the like. Other techniques include recording the noise in output signals due to temperature differences within an array using temperature reference sensors, as described in Rothberg et al. (published patent application cited above). Such noise may then be subtracted from the output signal in conventional signal processing techniques. However, all of these methods fail to actively control the overall system temperature and, therefore, they end up reducing the overall efficiency of the biological reaction.
In view of the above, it would be advantageous to have available a method and apparatus for controlling and optimizing the temperature of a system that includes a semiconductor sensor, so that it is matched biologically to what the reaction requires, by adjusting and monitoring the temperatures of the various components of the system.